A Trial to Explore the Potential Benefit of Safinamide on Cognitive Impairment Associated With Parkinson's Disease

Inclusion Criteria:

• Male or female outpatients (aged 45 to 80 years inclusive)

• Diagnosis of idiopathic Parkinson's Disease (PD) according to the UK PDS Brain BankCriteria and a Hoehn and Yahr Stage of I to III (mild to moderate motor severity) atScreening. The diagnosis will be based on medical history and neurological examination

• Subjects and informants must report cognitive impairment in at least one cognitivedomain on the PD Cognitive Questionnaire (PD-CQ).

• Cognitive impairment confirmed by a total score equal to- or below 26 on the MontrealCognitive Assessment (MoCA)

• Be able to speak, read, and write in the language in which the tests are written andmust be able to perform all the assessments in this language

• Receiving treatment with dopaminergic therapy (dopamine agonist and/or levodopa at astable dose for at least four weeks prior to Screening and for the duration of thestudy)

• Understand and sign the appropriate approved Informed Consent Form(s), one for thestudy (mandatory) and one for the pharmacogenetic evaluation (optional)

Exclusion Criteria:

• Any indication of forms of Parkinsonism other than idiopathic PD

• Diagnosis of PD Dementia (probable, possible) according to the Clinical DiagnosticCriteria for Dementia Associated with PD

• Diagnosis of Dementia with Lewy Bodies according to the McKeith criteria.

• Subjects with any clinically significant DSM-IV-TR Axis I Disorders including majordepression and severe anxiety; current diagnosis of substance abuse or history ofalcohol or drug abuse for 3 months prior to Visit 1 (Screening)

• Mental/physical/social condition which could preclude performing efficacy or safetyassessments

• Severe white matter disease, multiple lacunar infarcts, or signs of significantvascular changes on Magnetic Resonance Imaging (MRI)

• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or familymembers who suffer(ed) from such

• Current history of severe dizziness or fainting on standing, due to posturalhypotension

• Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolledatrial fibrillation, severe or unstable angina, congestive heart failure, myocardialinfarction in the three months prior to Visit 1 (Screening), or significantelectrocardiogram (ECG) abnormality, including heart-rate corrected interval QT (QTC) > 450 milliseconds (males) or > 470 milliseconds (females), with QTC based on theBazett's correction method

• Known diagnosis of human immunodeficiency virus (HIV) infection, positive results ontests for hepatitis B or C antibodies, or on tests for hepatitis B surface antigen (unless vaccinated)

• Neoplastic disease, either currently active or in remission for less than 1 year

• Clinically significant or unstable gastrointestinal, renal, hepatic, endocrine,pulmonary, or cardiovascular disease, including not well controlled hypertension,asthma, chronic obstructive pulmonary disease, and Type 1 diabetes that would, in theopinion of the Investigator, preclude participation to the study

• Any clinically relevant abnormality, either on medical history, physical andneurological examination, ECG, or by diagnostic laboratory tests that, in the opinionof the Investigator, could hinder participation to the study

• Currently experiencing end-of-dose wearing-off or on-off phenomena, disabling peakdose- or biphasic dyskinesia, or unpredictable or widely swinging fluctuations

• Any medical conditions and/or taking concomitant medications that could put them atrisk, interfere with study evaluations, or prevent meeting the requirements of thestudy

• Currently participating to another clinical trial or who participated in a previousclinical trial within 30 days prior to Visit 1 (Screening) or who received anyinvestigational product within 30 days or five half-lives, whichever was longer, priorto Visit 1 (Screening)

• Previously treated with safinamide

• Clinically significant hypertension or contraindications or hypersensitivity tomonoamine oxidase-Type B (MAO-B) inhibitors

• Anticholinergic medication and/or amantadine within 4 weeks prior to the Screeningvisit

• Opioids (e.g., tramadol and meperidine derivatives) or MAO inhibitors (e.g.,selegiline) within 8 weeks prior to Visit 1 (Screening) Dextromethorphan will beallowed to treat cough. One tricyclic- or tetracyclic antidepressant or trazodone willbe permitted if taken at bedtime at a low dose as a sleeping aid

• Acetylcholinesterase inhibitors or memantine within 4 weeks before start of the studytreatment or requiring these medications during the treatment period

• Depot neuroleptic during the study or within 1 injection cycle or oral neuroleptics (stable dose of quetiapine less than 100 mg/day for 8 weeks prior to Visit 1 will beallowed) within 4 weeks prior to Visit 1 (Screening)

• Drug that has hepatotoxic potential (e.g., tamoxifen) within 4 weeks prior to Visit 1 (Screening), or radiation therapy, or a drug with cytotoxic potential (e.g.,chemotherapy) within 1 year prior to the Screening visit.

• Subjects who, in the judgment of the Investigator, is likely to be non-compliant oruncooperative during the study

• Women who are pregnant, lactating, or who are attempting to conceive

• Women of childbearing potential not willing to use an adequate contraceptive method (unless surgically sterilized) for 4 weeks prior to, during, and 4 weeks after thelast dose of trial medication

• Clinically significant ophthalmologic abnormality such as patients with albinism,family history of hereditary retinal disease, progressive and/or severe diminution ofcorrected visual acuity, retinitis pigmentosa, any active retinopathy or ocularinflammation (uveitis), or progressive, severe diabetic retinopathy

• Known hypersensitivity to the trial treatment(s), including placebo or othercomparator drug(s)

• Legal incapacity or limited legal capacity